Pediatric Hypersensitivity Pneumonitis Workup

Updated: Jan 28, 2022
  • Author: Naga Jaya Smitha Yenduri, MD; Chief Editor: Girish D Sharma, MD, FCCP, FAAP  more...
  • Print

Approach Considerations

The most recent American Thoracic Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax (ATS/JRS/ALAT) guidelines on hypersensitivity pneumonitis published in August 2020 includes a proposed diagnostic algorithm by expert consensus that is helpful to make a provisional diagnosis in clinical practice. [75]


Laboratory Studies

Precipitating antibodies to the offending antigen are commonly present in hypersensitivity pneumonitis (HP); however it is not a specific finding as exposed persons without disease may have precipitating antibodies to the antigen. [76, 77] Reports have attributed missed diagnoses to false-negative results of precipitin studies, although repeat testing showed true-positive findings of precipitin in many cases. [78] The offending antigen may not be present on commonly used commercial hypersensitivity pneumonitis panels; sometimes a home inspection may be needed with immunodiffusion testing for the specific antigens found in the home.{ref98) See the image below.

Photograph reveals precipitin lines produced by me Photograph reveals precipitin lines produced by means of Ouchterlony immunodiffusion assay. Central wells contain the patient's serum. Peripheral wells contain serum or droppings from various birds. Reprinted with permission from Farber and Budson, 2000.

The erythrocyte sedimentation rate and C-reactive protein levels may be elevated, a rheumatoid factor may be present, and circulating immune complexes may be observed. However, these findings are not considered sufficiently specific to be useful for diagnosis. [70]

Hypergammaglobulinemia is a common finding but is neither sensitive nor specific.


Imaging Studies


Chest radiography is a useful first step because it is widely available, inexpensive, and can be used to screen for other cardiopulmonary disorders. However, chest radiography cannot be used to exclude hypersensitivity pneumonitis because normal chest radiography findings can be observed in subjects who meet other diagnostic criteria for hypersensitivity pneumonitis.

CT scanning

Chest CT scanning is more sensitive than chest radiography, and about 40% of cases of hypersensitivity pneumonitis with normal chest radiography findings show pulmonary abnormalities on chest CT scanning. The imaging findings depend on the phase of the disease, and findings of more than one phase may be observed if exposure to the causative antigen is ongoing. [79, 80]

Acute hypersensitivity pneumonitis

Nodular, ground glass, or consolidative airspace opacities resembling edema or infectious pneumonia can be seen on chest radiography or chest CT scanning in the acute setting, especially after heavy exposure to causative antigens. These opacities can be fleeting.

Subacute hypersensitivity pneumonitis

Imaging findings are similar to those observed in acute disease, with the additional chest CT scan findings of widespread, poorly-defined centrilobular ground-glass nodules corresponding to bronchiolocentric cellular interstitial pneumonia with poorly-formed granulomas on lung biopsy, and hyperlucent foci accentuated on expiratory images, corresponding to sites of air trapping. See the images below.

14-year-old girl with subacute hypersensitivity pn 14-year-old girl with subacute hypersensitivity pneumonitis from avian antigen exposure. Chest radiograph demonstrates numerous tiny pulmonary nodules bilaterally.
Chest CT from same patient as previous image revea Chest CT from same patient as previous image reveals widespread poorly-defined centrilobular ground-glass nodules related to bronchiolocentric cellular interstitial pneumonia with poorly-formed granulomas.

Chronic hypersensitivity pneumonitis

Chest CT scanning may reveal ground-glass pulmonary opacities without or with findings of pulmonary fibrosis, such as reticular pulmonary opacities, architectural distortion, traction bronchiectasis, honeycombing, or volume loss. See the image below.

A 10-year-old girl with chronic hypersensitivity p A 10-year-old girl with chronic hypersensitivity pneumonitis from avian antigen exposure. Chest CT image shows reticular pulmonary opacities and architectural distortion at the lung bases indicative of pulmonary fibrosis.

Imaging results

The imaging findings of acute and subacute hypersensitivity pneumonitis may take several weeks to resolve with treatment. The chest CT findings of pulmonary fibrosis persist despite elimination of exposure to the causative antigen and provide important prognostic information. [81]

Pulmonary hypertension has been reported in older adults with advanced chronic hypersensitivity pneumonitis complicated by moderate to severe pulmonary restriction and hypoxemia on room air. [82] Given this finding, screening children with severe chronic hypersensitivity pneumonitis for pulmonary hypertension using Doppler echocardiography is reasonable.


Other Tests

Pulmonary function studies

Acute hypersensitivity pneumonitis

Pulmonary function may be normal between acute episodes of hypersensitivity pneumonitis. Normal diffusing capacity observed between exacerbations of acute or subacute hypersensitivity pneumonitis does not exclude the diagnosis. Testing during acute episodes of hypersensitivity pneumonitis reveals predominately restrictive changes; however, obstruction and bronchial hyperreactivity can also be seen. Obstruction alone does not preclude a diagnosis of hypersensitivity pneumonitis. Hypoxemia can be seen in patients with active pneumonitis whether the affected patient is at rest or exercising. [34]

Subacute hypersensitivity pneumonitis

Pulmonary function testing may demonstrate mild hypoxemia, restriction and/or obstruction, and a reduced capacity for diffusing carbon monoxide.

Chronic hypersensitivity pneumonitis

A reduced diffusing capacity of the lung for carbon monoxide may be the earliest abnormality observed. Pulmonary restriction, hypoxemia at rest, and/or desaturation during the 6-minute walk test indicates the presence of more advanced disease.

Provocation challenge

The role of inhalation challenge is controversial because it can provoke clinically significant disease and standardized antigen preparations are not yet available. Because of the risk for the late-phase severe reactions, patients should be closely observed for at least 24 hours after the inhalation challenge is administered. [83]

Natural challenge

The development of signs and symptoms after the patient is re-exposed to the antigenic environment supports a diagnosis of acute or subacute hypersensitivity pneumonitis.

Skin testing

Skin testing is not helpful in assessing hypersensitivity pneumonitis. [84]



Analysis of bronchoalveolar lavage (BAL) fluid (BALF) is the most sensitive tool for alveolitis detection in patients with suspected hypersensitivity pneumonitis. Analysis of BALF in hypersensitivity pneumonitis typically reveals the following [15, 83] :

  • Lymphocytosis (>20% of WBCs recovered)

  • Elevated proportion of neutrophils (may be elevated to >5%), especially after recent antigenic exposure or in advanced disease

  • Elevated proportion of eosinophils (may be >5%), particularly in advanced disease

Analysis of bronchoalveolar lavage fluid in adults with hypersensitivity pneumonitis frequently reveals a CD4/CD8 ratio of less than 1. As stated above (see Pathophysiology), children naturally have a low CD4/CD8 ratio due to an elevated number of CD8 cells. Thus, this finding is neither sensitive nor specific for hypersensitivity pneumonitis in children. [85, 86]

One study of BALF cytology reported that adults with hypersensitivity pneumonitis have a greater percentage of natural killer T cells than adults with sarcoidosis. [13] The natural killer T cells observed in patients with hypersensitivity pneumonitis were predominantly of the CD8+CD56+ population. The clinical use of this observation has yet to be determined.

Induced sputum has been proposed as a noninvasive alternative to BAL. In adults with hypersensitivity pneumonitis, the distribution of T-cell subpopulations is similar in induced sputum and BALF; however the percentage of lymphocytes was substantially lower in the induced sputum. [87] Although lymphocytosis and elevated proportion of CD8+ cells on induced sputum is consistent with hypersensitivity pneumonitis, induced sputum should not be relied on to exclude the diagnosis.

Lung biopsy can be considered if the diagnosis cannot be established by other less-invasive methods. The role of transbronchial biopsy is controversial, with some authors advocating it as a less invasive test; [83] others are much less enthusiastic because the diagnostic yield is poor and interpretation is not consistent. [88] The extent to which invasive testing should be performed should be based on the probability of the diagnosis, the impact on patient and family of making the diagnosis, and the need to rule out alternative diagnoses. [12] Examples of lung biopsy findings are shown in the images below.

Photomicrograph of a lung biopsy specimen reveals Photomicrograph of a lung biopsy specimen reveals marked interstitial inflammation with lymphocytic predominance and a multinucleated giant cell (hematoxylin-eosin stain, original magnification 40X). Reprinted with permission from Farber and Budson, 2000.
Photomicrograph of a lung biopsy sample reveals in Photomicrograph of a lung biopsy sample reveals interstitial fibrosis with active interstitial inflammation (hematoxylin-eosin stain, original magnification 10X). Reprinted with permission from Farber and Budson, 2000.

Histologic Findings

Hypersensitivity pneumonitis is a diffuse, predominantly mononuclear cell inflammation of the small airways and pulmonary parenchyma. The inflammation is often associated with poorly formed, nonnecrotizing granulomas. [89] A bronchiolocentric distribution of the interstitial inflammation is believed to result from the airway being the portal of entry for the offending agent. Histologic findings may include the following [90, 91] :

  • Bronchiolocentric, chronic interstitial inflammation in which lymphocytes predominate

  • Poorly formed, noncaseating necrotizing interstitial granulomas

  • Foamy macrophages within airspaces

  • Intra-alveolar foci of organizing pneumonia

  • Dense fibrosis, honeycombing, and fibroblastic foci in advanced, chronic disease with potential upper lobe contraction.

Nonclassic and nonspecific pathology has been described in patients who otherwise met criteria for hypersensitivity pneumonitis. Cases of clinical hypersensitivity pneumonitis have been documented with biopsy results showing only nonspecific interstitial pneumonitis (NSIP) or a bronchiolitis obliterans organizing pneumonia (BOOP)–like picture. [15, 92]